Evidence map›Paper›PMID 24978642›Full record

ArticleLaboratory investigation; a journal of technical methods and pathology2014

Erythropoietin protects against hemorrhagic blood-brain barrier disruption through the effects of aquaporin-4.

Heling Chu, Hongyan Ding, Yuping Tang, Qiang Dong

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Laboratory investigation; a journal of technical methods and pathology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
4.9field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Aquaporin-4 in Stroke and Brain Edema-Friend or Foe?International journal of molecular sciences · 2025
    Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Aquaporin-4 and Cognitive Disorders.Aging and disease · 2022
    Review
  14. Review
  15. Article
  16. Article
  17. Review
  18. Review
  19. Review
  20. Insights into Potential Targets for Therapeutic Intervention in Epilepsy.International journal of molecular sciences · 2020
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Heling ChuDepartment of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
Hongyan DingDepartment of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
Yuping TangDepartment of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
Qiang DongDepartment of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
Huashan Hospital · CNFudan University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Erythropoietin (EPO) has protective effects against many neurological diseases, including intracerebral hemorrhage (ICH). Here, we aimed to test EPO's effects on blood-brain barrier (BBB) disruption morphologically and functionally following ICH, which has not been well investigated. We also examined whether the effects were dependent on aquaporin-4 (AQP4). We detected the expression of perihematomal AQP4 and EPO receptor (EPOR) induced by EPO injection at 1, 3 and 7 days after ICH. We also examined the effects of EPO on BBB disruption by ICH in wild-type mice, and tested whether such effects were AQP4 dependent by using AQP4 knock-out mice. Furthermore, we assessed the related signal transduction pathways via astrocyte cultures. We found that EPO highly increased perihematomal AQP4 and EPOR expression. Specifically, EPO led to BBB protection in both types of mice by functionally reducing brain edema and BBB permeability, as well as morphologically suppressing tight junction (TJ) opening and endothelial cell swelling, and increasing expression of the TJ proteins occludin and zonula occluden-1 (ZO-1). Statistical analysis indicated that AQP4 was required for these effects. In addition, EPO upregulated phosphorylation of C-Jun amino-terminal kinase (JNK) and p38-mitogen-activated protein kinase (MAPK) as well as EPOR and AQP4 proteins in cultured astrocytes. The latter was inhibited by JNK and p38-MAPK inhibitors. Our data suggest that EPO protects BBB from disruption after ICH and that the main targets are the TJ proteins occludin and ZO-1. The effects of EPO are associated with increased levels of AQP4, and may occur through activation of JNK and p38-MAPK pathways after binding to EPOR.

Indexed as

AnimalsAquaporin 4AstrocytesBlood-Brain BarrierBlotting, WesternCells, CulturedErythropoietinFluorescent Antibody TechniqueMaleMiceMice, TransgenicMicroscopy, ElectronPhosphorylationSignal TransductionTight JunctionsAquaporin 4Erythropoietin

Identifiers

PMID24978642
OpenAlexW2073623008

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.